Antifungal drugs: An updated review of central nervous system pharmacokinetics

Mycoses. 2020 Oct;63(10):1047-1059. doi: 10.1111/myc.13157. Epub 2020 Sep 4.

Abstract

Invasive fungal infections (IFIs) in the central nervous system (CNS) are particularly hard to treat and are associated with high morbidity and mortality rates. Four chemical classes of systemic antifungal agents are used for the treatment of IFIs (eg meningitis), including polyenes, triazoles, pyrimidine analogues and echinocandins. This review will address all of these classes and discuss their penetration and accumulation in the CNS. Treatment of fungal meningitis is based on the antifungal that shows good penetration and accumulation in the CNS. Pharmacokinetic data concerning the entry of antifungal agents into the intracranial compartments are faulty. This review will provide an overview of the ability of systemic antifungals to penetrate the CNS, based on previously published drug physicochemical properties and pharmacokinetic data, for evaluation of the most promising antifungal drugs for the treatment of fungal CNS infections. The studies selected and discussed in this review are from 1990 to 2019.

Keywords: antifungal agents; blood-brain barrier; central nervous system; invasive fungal infections; pharmacokinetic.

Publication types

  • Review

MeSH terms

  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / therapeutic use
  • Central Nervous System Fungal Infections / drug therapy*
  • Echinocandins / pharmacokinetics
  • Echinocandins / therapeutic use
  • Humans
  • Invasive Fungal Infections / drug therapy
  • Meningitis, Fungal / drug therapy
  • Polyenes / pharmacokinetics
  • Polyenes / therapeutic use
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / therapeutic use
  • Triazoles / pharmacokinetics
  • Triazoles / therapeutic use

Substances

  • Antifungal Agents
  • Echinocandins
  • Polyenes
  • Pyrimidines
  • Triazoles